OC-0235: Enhancing stereotactic radiation schedules using the vascular disrupting agent OXi4503

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Effect of the second-generation vascular disrupting agent OXi4503 on tumor vascularity.

PURPOSE As first-generation small-molecule vascular disrupting agents (VDA) have begun to enter clinical trials, second-generation agents are under active development. One such agent is the combretastatin A4 disodium phosphate (CA4P) analogue OXi4503 (CA1P). EXPERIMENTAL DESIGN C3H/HeJ mice bearing KHT sarcomas were treated with CA4P and OXi4503 and the effect on tumor vasculature was determi...

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Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer

Vascular disrupting agents (VDAs) represent a relatively distinct class of agents that target established blood vessels in tumors. In this study, we examined the preclinical activity of the second-generation VDA OXi4503 against human head and neck squamous cell carcinoma (HNSCC). Studies were performed in subcutaneous and orthotopic FaDu-luc HNSCC xenografts established in immunodeficient mice....

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Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors.

PURPOSE Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents. EXPERIMENTAL DESIGN Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors. RESULTS Doses were escalated in single-patient cohorts from 0.06 to 1....

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Dual targeting of tumor vasculature: combining Avastin and vascular disrupting agents (CA4P or OXi4503).

BACKGROUND This study evaluated the therapeutic efficacy of combining vascular disrupting agents with antiangiogenic agents. MATERIALS AND METHODS Human clear cell renal carcinoma (Caki-1) tumors were established in nude mice. Treatments consisted of Avastin (2 mg/kg) administered twice a week; CA4P (100 mg/kg) or OXi4503 (25 mg/kg) administered 3 times a week for a period of 2 weeks; or a co...

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Our previous studies demonstrated arsenic trioxide- (ATO-) induced selective tumor vascular disruption and augmentation of thermal or radiotherapy effect against solid tumors. These results suggested that a trimodality approach of radiation, ATO, and local hyperthermia may have potent therapeutic efficacy against solid tumors. Here, we report the antitumor effect of hypofractionated radiation f...

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ژورنال

عنوان ژورنال: Radiotherapy and Oncology

سال: 2016

ISSN: 0167-8140

DOI: 10.1016/s0167-8140(16)31484-0